Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Automated scans let scientists track drugs’ broad effects on cells

12.11.2004


’Cytological profiling’ could streamline early phases of drug discovery

Bringing an unprecedented level of automation to microscopy, scientists at Harvard University have developed a powerful new method of visualizing drugs’ multifaceted impact on cells. The technique, which could eventually become a standard tool for drug discovery, is described this week in the journal Science.

Steven J. Altschuler and Lani F. Wu, mathematicians skilled in developing models to find meaningful patterns among mountains of data, worked with Timothy J. Mitchison of Harvard Medical School to automate microscopic imaging of drug-treated cells and recast the resulting scans in a computer-friendly format. The result: a method dubbed "cytological profiling" that trains computers to recognize cell status and health from cellular images, virtually automating microscopic scanning for various types of abnormalities.



"The resulting profiles of cellular changes wrought by drugs at various dosages provide information on drug mechanism that is highly relevant to understanding the specificity and toxicity of drugs," says Altschuler, research fellow at the Bauer Center for Genomics Research in Harvard’s Faculty of Arts and Sciences. "The information gleaned includes many key indicators of drugs’ potential usefulness and limitations as medicines."

"We actually started out on this project thinking that this could be a good research tool," adds Wu, research fellow at the Bauer Center. "We’ve now discovered, to our surprise, that it may also prove a powerful tool for drug discovery."

High-throughput cytological profiling lets scientists test numerous variables at once, wringing countless discrete cellular measurements from a single experiment. Faced with scores of drugs holding the potential to combat a given disease, researchers could hone in on the most promising drugs in a fraction of the time of current methods.

"This technique employs ’guilt by association’ -- if two drugs’ cytological profiles look similar, they probably work through similar mechanisms," Altschuler says. "It’s particularly useful for understanding drug action because it allows us to look at many concentrations of a drug, which is essential for comparing two drugs that may have different potency but act on the same target."

Since they are hardy and flourish even outside the body, the Harvard team used human cancer cells. They placed the cells in 384 minuscule wells in a plastic dish, injected each well with one of 100 drugs -- both medicines and toxins -- at different concentrations, and finished off the plates with11 chemical probes for different proteins and DNA.

After 20 hours of cell growth, the researchers used automated microscopy to collect some half a million images of the treated cells, followed by approximately 5 billion individual measurements of the size, shape, and quantity of different proteins, DNA, and organelles in each. Software developed by Altschuler, Wu, and colleagues allowed them to convert this copious data into profiles of the effects of each drug, yielding distinctive red-and-green "fingerprints" for each, not unlike the color-coded data from a DNA chip.

However, unlike DNA chips that meld bountiful data into an "average" denoted by dots of color on a grid, cytological profiling preserves individual data points -- so researchers can go back and analyze fine-grain information.

"By allowing quantitative measurement of many proteins and structures in cells over many samples, and systematic comparison between samples, our method brings microscopy into the ’-omics’ era, like genomics and proteomics," says Mitchison, of Harvard Medical School’s Institute of Chemistry and Cell Biology and Department of Systems Biology. "This really allows us a much broader view of how cells are affected by a wide range of perturbations."

Cytological profiling may be especially useful, Mitchison says, for evaluating drug candidatesin areas where making a drug with a highly specific biochemical effect is difficult, such as kinase inhibitors. Future applications may include testing the response of cancer cells with different genetic profiles to a spectrum of anti-cancer drugs, which could help predict clinical responses in individual patients.
Alschuler, Wu, and Mitchison were joined in this research, sponsored by the National Cancer Institute and Howard Hughes Medical Institute, by co-authors Zachary E. Perlman and Yan Feng at Harvard Medical School and Michael D. Slack in the Bauer Center for Genomics Research.

Steve Bradt | EurekAlert!
Further information:
http://www.harvard.edu

More articles from Life Sciences:

nachricht New photocatalyst speeds up the conversion of carbon dioxide into chemical resources
29.05.2017 | DGIST (Daegu Gyeongbuk Institute of Science and Technology)

nachricht Copper hydroxide nanoparticles provide protection against toxic oxygen radicals in cigarette smoke
29.05.2017 | Johannes Gutenberg-Universität Mainz

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Strathclyde-led research develops world's highest gain high-power laser amplifier

The world's highest gain high power laser amplifier - by many orders of magnitude - has been developed in research led at the University of Strathclyde.

The researchers demonstrated the feasibility of using plasma to amplify short laser pulses of picojoule-level energy up to 100 millijoules, which is a 'gain'...

Im Focus: Can the immune system be boosted against Staphylococcus aureus by delivery of messenger RNA?

Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.

Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....

Im Focus: A quantum walk of photons

Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.

The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....

Im Focus: Turmoil in sluggish electrons’ existence

An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.

We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...

Im Focus: Wafer-thin Magnetic Materials Developed for Future Quantum Technologies

Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.

Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Marine Conservation: IASS Contributes to UN Ocean Conference in New York on 5-9 June

24.05.2017 | Event News

AWK Aachen Machine Tool Colloquium 2017: Internet of Production for Agile Enterprises

23.05.2017 | Event News

Dortmund MST Conference presents Individualized Healthcare Solutions with micro and nanotechnology

22.05.2017 | Event News

 
Latest News

New insights into the ancestors of all complex life

29.05.2017 | Earth Sciences

New photocatalyst speeds up the conversion of carbon dioxide into chemical resources

29.05.2017 | Life Sciences

NASA's SDO sees partial eclipse in space

29.05.2017 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>